Assisted reproduction mediated resurrection of a feline model for Chediak-Higashi syndrome caused by a large duplication in LYST.

Chediak-Higashi Syndrome (CHS) is a well-characterized, autosomal recessively inherited lysosomal disease caused by mutations in lysosomal trafficking regulator (LYST). The feline model for CHS was originally maintained for ~20 years. However, the colonies were disbanded and the CHS cat model was lost to the research community before the causative mutation was identified. To resurrect the cat model, semen was collected and cryopreserved from a lone, fertile,  CHS carrier male. Using cryopreserved semen, laparoscopic oviductal artificial insemination was performed on three queens, two queens produced 11 viable kittens. To identify the causative mutation, a fibroblast cell line, derived from an affected cat from the original colony, was whole genome sequenced. Visual inspection of the sequence data identified a candidate causal variant as a ~20 kb tandem duplication within LYST, spanning exons 30 through to 38 (NM_001290242.1:c.8347-2422_9548 + 1749dup). PCR genotyping of the produced offspring demonstrated three individuals inherited the mutant allele from the CHS carrier male. This study demonstrated the successful use of cryopreservation and assisted reproduction to maintain and resurrect biomedical models and has defined the variant causing Chediak-Higashi syndrome in the domestic cat.

Temporal changes in serum luteinizing hormone following ovariohysterectomy and gonadotropin-releasing hormone vaccination in domestic cats.

Measurement of circulating luteinizing hormone (LH) concentrations in cats and temporal changes following ovariohysterectomy (OHE) or possibly GnRH vaccination may be informative for assessing their fertility, contraception or sterilization status. In this study, serum LH concentrations were measured in domestic cats (n = 6) immediately prior to and up to 120 days post-OHE. Basal LH concentrations of females previously subjected to OHE (n = 4; ~1.5 years post-OHE) were compared pre- and post-vaccination with a GnRH immunocontraceptive, and to LH concentrations in intact females. Basal serum LH concentrations (2.67 ± 0.43 ng/ml; mean ± SEM) in intact females increased (p < .01) by 30 days post-OHE (5.65 ± 0.87 ng/ml) but then declined (p < .05) to pre-OHE levels (mean range, 3.26-3.62 ng/ml) at days 60-120 post-OHE. Serum LH (3.84 ± 0.51 ng/ml) in four females ~1.5 years after OHE tended to be higher (p = .10) than those of intact females prior to OHE. Three months following first or second GnRH immunocontraceptive vaccine treatment, serum LH values in females previously subjected to OHE decreased (p < .05) to concentrations similar to those observed in intact females. Our preliminary results suggest that OHE of domestic cats causes a marked increase in basal LH levels within the first few weeks after ovariohysterectomy followed by a return to pre-OHE basal values over the next several months. Reduced LH concentrations after GnRH vaccine may indicate the effectiveness of the immunocontraceptive in reducing the circulating levels of GnRH, thereby reducing secretion of LH.

Comparative fertility of freshly collected vs frozen-thawed semen with laparoscopic oviductal artificial insemination in domestic cats.

Artificial insemination (AI) is potentially invaluable as an adjunct to natural breeding for the conservation management of non-domestic felid populations. The efficacy of AI, however, must be substantially improved for applied use, especially when using frozen semen. Our recent advances in using laparoscopic oviductal AI (LO-AI) with low sperm numbers and freezing of cat semen in a soy lecithin-based cryoprotectant medium suggest that combining these two approaches might improve pregnancy outcomes with frozen-thawed spermatozoa. In this study, our objectives were to (i) assess the effect of two gonadotropin dosages (100 vs 150 IU eCG) on ovarian response in domestic cats and (ii) compare the relative fertility of frozen-thawed and fresh semen in vivo following LO-AI. All 16 females ovulated after gonadotropin treatment and were inseminated with fresh semen from one male and frozen-thawed semen from a second male. There were no differences between gonadotropin dosages in CL number, pregnancy percentage or litter size. Half (8/16) of the females conceived, with seven females giving birth to a total of 36 offspring. Paternity analysis showed that more kittens resulted from LO-AI with fresh (28/36, 78%) than frozen-thawed (8/36, 22%) semen, possibly due to impaired motility and longevity of thawed sperm. These results demonstrated that viable offspring can be produced by AI using semen frozen in a soy lecithin-based medium. Insemination with greater numbers of frozen-thawed spermatozoa, combined with further refinement of cat sperm cryopreservation methods, may be necessary to optimize pregnancy success with LO-AI in domestic and nondomestic cats.

Demographic and psychosocial correlates of physical activity in late life.

INTRODUCTION: According to the Centers for Disease Control and Prevention and the World Health Organization, increasing physical activity may help prolong health and preserve the quality of life in late adulthood. Physical activity has taken center stage as the behavior most likely to alter health. However, there is little recent population-wide information about the demographic and psychosocial correlates of physical activity in the elderly population. The purpose of the study was to identify the factors associated with older adults' frequency of physical activity. The study may have implications for preventive interventions. METHODS: Data for 12,611 community-dwelling people aged > or = 65 from the 1996-1997 Canadian National Population Health Survey were examined. Predictors of frequent versus infrequent self-reported physical activity lasting > 15 minutes were examined using logistic regression analyses. The predictor variables included geographic location, psychological distress (Generalized Distress Scale), demographic factors (age, gender, educational level, and marital status), perceived social support, chronic medical conditions, physical limitations due to injury, functional limitations, smoking behavior, and body mass index (BMI). RESULTS: Gender (male); younger age; higher levels of education; being unmarried; absence of chronic conditions, injuries, and functional limitations; lower BMI; social support (females); nonsmoking; region; and lower levels of psychological distress were associated with frequent physical activity in late life. Older adults in western Canadian provinces were more active than those in eastern provinces. CONCLUSIONS: The results will be useful for the design of interventions aimed at improving older adults' health behavior and other health and functional outcomes, especially for subgroups in particular need. Recommendations for further longitudinal research are presented.

An evaluation of smoking cessation-related activities by pharmacists.

OBJECTIVES: To (1) describe the types of smoking cessation intervention activities performed by community pharmacists and (2) assess the perceived barriers to this type of intervention. DESIGN: Confidential mail questionnaire. SETTING AND PARTICIPANTS: 541 community pharmacists in North Carolina and 946 community pharmacists in Texas. RESULTS: North Carolina and Texas differ with respect to the sale of cigarettes at the practice site, with North Carolina pharmacies being more likely to sell tobacco products. Overall, 555 (92.5%) respondents reported that they do not routinely ask new patients if they smoke or use tobacco products. Pharmacists described themselves as knowledgeable about smoking cessation therapies, and 42% of respondents had attended an educational program on smoking cessation. A total of 230 (39.5%) reported consistently counseling individual patients about smoking cessation treatment strategies on at least a weekly basis. Exploratory factor analysis identified four dimensions of barriers that inhibit pharmacists from engaging in smoking cessation-related activities: (1) pharmacist interpersonal characteristics, (2) practice site considerations, (3) patient characteristics, and (4) financial concerns. CONCLUSION: Pharmacists have an opportunity to identify health risks and counsel patients about disease-preventing lifestyle changes. These findings suggest that although pharmacists believe they are qualified to perform smoking cessation interventions, they do not routinely identify smokers and they perceive several barriers to participating in such activities. Pharmacists should investigate increased involvement in smoking cessation activities for the benefit of their patients and for the potential professional and economic rewards.

Stability and change in older adults' social contact and social support: the Cardiovascular Health Study.

OBJECTIVES: The aim of this study was to examine the degree of individual change in structural indicators of social support (family network contact and close friend network contact) and functional indicators of social support (belonging, appraisal, and tangible support) during late life. METHODS: Using a large population-based sample of older adults, hierarchical linear modeling was applied to examine the extent of change in social contact and support as well as sociodemographic characteristics (age, race, gender, and education) that might explain individual variability in contact and support at baseline and over time. RESULTS: Consistent with predictions, small yet significant increases were observed in belonging support and tangible support. Contrary to predictions, no evidence was found for significant individual change in family network contact, close friend network contact, or appraisal support. Sociodemographic characteristics were more consistent predictors of variability in contact and support at baseline than variability over time. DISCUSSION: The findings of this study add to a growing literature suggesting that late life is not typically characterized by a decline in important social resources.

Correlates and prevalence of benzodiazepine use in community-dwelling elderly.

OBJECTIVE: To describe the prevalence of benzodiazepine use, sociodemographic and physical health factors associated with use, dosages taken, and directions for use among individuals aged 65 years and older. DESIGN: Cross-sectional analysis of baseline data from the community-based, prospective observational Cardiovascular Health Study. PATIENTS/PARTICIPANTS: Medicare eligibility lists from four U.S. communities were used to recruit a representative sample of 5,201 community-dwelling elderly, of which 5,181 participants met all study criteria. MEASUREMENTS AND MAIN RESULTS: Among participants, 511 (9.9%) were taking at least one benzodiazepine, primarily anxiolytics (73%). Benzodiazepines were often prescribed to be taken pro re nata (PRN "as needed"), and 36.5% of prescriptions with instructions to be taken regularly were taken at a dose lower than prescribed. Reported over-the-counter (OTC) sleep aid medication use was 39.2% in benzodiazepine users and 3.3% in nonusers. In a multivariate logistic model, the significant independent correlates of benzodiazepine use were being white (odds ratio [OR] 1.9; 95% confidence interval [CI] 1.0, 3.4), female (OR 1.7; CI 1.4, 2.2), and living in Forsyth County, North Carolina, or Washington County, Maryland, compared with living in Sacramento County, California, or Allegheny County, Pennsylvania (OR 2.3; CI 1.4, 2.2); having coronary heart disease (OR 1.6; CI 1.2, 2.1), health status reported as poor or fair (OR 1.8; CI 1.4, 2.3), self-reported diagnosis of nervous or emotional disorder (OR 6.7; CI 5.1, 8.7), and reporting use of an OTC sleep aid medication (OR 18.7; CI 14.1, 24.7). CONCLUSIONS: One in 10 participants reported taking a benzodiazepine, most frequently an anxiolytic, often at a lower dose than prescribed and usually PRN. The high prevalence of OTC sleep aid medication and benzodiazepine use may place the patient at increased risk of psychomotor impairment. Physicians should assess OTC sleep aid medication use when prescribing benzodiazepines.

Caregiving from the recipient's perspective: negative reactions to being helped.

This study investigated predictors of negative reactions to assistance provided to a physically disabled spouse (n = 276, M age: 76.6 years) and the consequences that negative reactions may have for the mental health of the care recipient. Nearly 40% of recipients reported some emotional distress in response to help they received. Fatalistic attitudes, perceived control, and lower self-esteem predicted greater helping distress, whereas lower self-esteem, fatalistic beliefs, and marital conflict were especially likely to lead to helping distress for those who received higher levels of assistance. Helping distress was also found to predict depression as much as 1 year later, suggesting that there may be long-term consequences of negative reactions to assistance. These findings have important implications for the study of caregiving and the relationship between physical impairment and depression.

Traumatic grief as a risk factor for mental and physical morbidity.

OBJECTIVE: The aim of this study was to confirm and extend the authors' previous work indicating that symptoms of traumatic grief are predictors of future physical and mental health outcomes. METHOD: The study group consisted of 150 future widows and widowers interviewed at the time of their spouse's hospital admission and at 6-week and 6-, 13-, and 25- month follow-ups. Traumatic grief was measured with a modified version of the Grief Measurement Scale. Mental and physical health outcomes were assessed by self-report and interviewer evaluation. Survival analysis and linear and logistic regressions were used to determine the risk for adverse mental and physical health outcomes posed by traumatic grief. RESULTS: Survival and regression analyses indicated that the presence of traumatic grief symptoms approximately 6 months after the death of the spouse predicted such negative health outcomes as cancer, heart trouble, high blood pressure, suicidal ideation, and changes in eating habits at 13- or 25-month follow-up. CONCLUSIONS: The results suggest that it may not be the stress of bereavement, per se, that puts individuals at risk for long-term mental and physical health impairments and adverse health behaviors. Rather, it appears that psychiatric sequelae such as traumatic grief are of critical importance in determining which bereaved individuals will be at risk for long-term dysfunction.

Health effects of caregiving: the caregiver health effects study: an ancillary study of the Cardiovascular Health Study.

We propose that two related sources of variability in studies of caregiving health effects contribute to an inconsistent pattern of findings: the sampling strategy used and the definition of what constitutes caregiving. Samples are often recruited through self-referral and are typically comprised of caregivers experiencing considerable distress. In this study, we examine the health effects of caregiving in large population-based samples of spousal caregivers and controls using a wide array of objective and self-report physical and mental health outcome measures. By applying different definitions of caregiving, we show that the magnitude of health effects attributable to caregiving can vary substantially, with the largest negative health effects observed among caregivers who characterize themselves as being strained. From an epidemiological perspective, our data show that approximately 80% of persons living with a spouse with a disability provide care to their spouse, but only half of care providers report mental or physical strain associated with caregiving.

Preventive health behaviors among spousal caregivers.

BACKGROUND: The physical and emotional burden of caring for a functionally impaired spouse may adversely affect the preventive health behavior of the caregiver. This study explores the relationship between caregiving and lifestyle health behaviors and use of preventive services. METHODS: The Caregiver Health Effects Study identified spousal caregivers among a sample of more than 3,000 married, community-dwelling older persons, from four counties in the United States, who were enrollees in the Cardiovascular Health Study. High-level caregivers were defined as having a spouse with an ADL impairment (n = 212) and moderate-level caregivers, a spouse with one or more IADL impairments (n = 222). For each caregiver, a control, matched for age and gender, was selected (n = 385). Structured interviews were conducted in the home, following enrollment. RESULTS: Being a high-level caregiver significantly increased the odds of not getting enough rest, not having enough time to exercise, not having time to rest to recuperate from illness, and forgetting to take prescription medications, compared with noncaregivers. These findings did not hold for moderate-level caregivers. The odds were not significantly different for either level of caregiver compared with noncaregivers for missing meals, missing doctor appointments, missing flu shots, and not refilling medications. Larger proportions of caregivers with a strong sense of control had good preventive health behaviors, compared with caregivers with a weak sense of control.

Complicated grief as a disorder distinct from bereavement-related depression and anxiety: a replication study.

OBJECTIVE: This study sought to confirm in an independent, nonclinical study group previous work which demonstrated that the symptoms of complicated grief were distinct from the symptoms of bereavement related depression and anxiety. METHOD: Data used in the analyses were derived from a group of 150 widowed individuals who were interviewed 6 months after their deceased spouses' hospital admission (study entry). Complicated grief was measured with a modified version of the Grief Measurement Scale. Principal axis factoring was used to determine the distinctiveness of complicated grief, depression, and anxiety. RESULTS: The principal axis factoring showed that the symptoms of complicated grief loaded quite highly on the first (complicated grief) factor and loaded very poorly on the anxiety and depression factors. CONCLUSIONS: The results confirmed the authors' previous findings demonstrating the distinction between symptoms of complicated grief and symptoms of bereavement-related depression and anxiety.

Longitudinal analysis of specific domains of internal control and depressive symptoms in patients with recurrent cancer.

The relation between perceptions of control and depressive symptoms was examined in a longitudinal study of patients with recurrent cancer. Five domains of control (self-blame, control over cancer onset, control over symptoms, control over the course of the illness, and overall control over life events) were found to be independent of one another. In cross-sectional analyses, depression symptomatology was negatively correlated with illness course control, symptom control, and overall control. Cross-lagged longitudinal analyses using structural equation modeling suggested only onset control and overall control were significantly associated with depressive symptomatology over the 8-month interval. Greater baseline onset control predicted greater follow-up depression, whereas higher baseline depression predicted lower follow-up overall control. The importance of developing and using domain-specific measures of control and investigating the association of control and adjustment in longitudinal analysis are discussed.

Health downturns and predictors of suicidal ideation: an application of the Baumeister model.

Suicidal thoughts and attempts have been studied from a number of perspectives, but only recently has an attempt been made to incorporate many different psychological perspectives into one framework. Baumeister (1990) has integrated personality and social psychological perspectives into one sequential model, moving from instigating events to a final stage of suicidal thoughts. Employing a sample of older adult subjects undergoing the stresses of a recent health downturn, this study tested a four-stage model of suicidal ideation based on many of the components proposed by Baumeister. Structural equation modeling achieved a good fit to the data. Results are discussed in terms of the importance of including life events, particularly poor health, and cognitive variables such as confusions in thinking, in understanding suicidal ideation.

Anxiety among widowed elders: is it distinct from depression and grief?

The purpose of this study was to test the validity and utility of distinguishing symptoms of anxiety from those of depression and grief in recently spousally bereaved elders. We also examined pathways from baseline (six months or less post-spousal death) to follow-up (12 and 18 months post-death) levels of anxiety, depression and grief-related symptoms. Baseline and follow-up data were available from 56 recently widowed elderly subjects recruited for an investigation of physiological changes in bereavement. Confirmatory factor analyses indicated that a model in which anxiety was specified as a third factor, apart from depression and grief factors, fit the data well and significantly better than either the one or two factor models. Path analyses revealed that both baseline severity of grief and anxiety had significant lagged effects and predicted follow-up severity of depression. Symptoms of anxiety appeared distinct from those of depression and grief, and the anxiety, depression and grief factors differentially predicted subsequent symptomatology. These findings suggest a need for more specific identification and treatment of anxiety, depression and grief symptoms within the context of late-life spousal bereavement.

Inventory of Complicated Grief: a scale to measure maladaptive symptoms of loss.

Certain symptoms of grief have been shown (a) to be distinct from bereavement-related depression and anxiety, and (b) to predict long-term functional impairments. We termed these symptoms of "complicated grief" and developed the Inventory of Complicated Grief (ICG) to assess them. Data were derived from 97 conjugally bereaved elders who completed the ICG, along with other self-report scales measuring grief, depression, and background characteristics. Exploratory factor analyses indicated that the ICG measured a single underlying construct of complicated grief. High internal consistency and test-retest reliabilities were evidence of the ICG's reliability. The ICG total score's association with severity of depressive symptoms and a general measure of grief suggested a valid, yet distinct, assessment of emotional distress. Respondents with ICG scores > 25 were significantly more impaired in social, general, mental, and physical health functioning and in bodily pain than those with ICG scores < or = 25. Thus, the ICG, a scale with demonstrated internal consistency, and convergent and criterion validity, provides an easily administered assessment for symptoms of complicated grief.

State and trait negative affect as predictors of objective and subjective symptoms of respiratory viral infections.

State and trait negative affect (NA) were measured in healthy people immediately before an illness was induced through exposure to a respiratory virus. State NA, disease-specific health complaints (e.g., runny nose, congestion, and sneezing), and an associated objective marker of disease severity (mucus secretion weights) were assessed daily during the illness. Baseline trait and state NA were both associated with increased numbers of subsequent complaints. Although greater numbers of complaints among people high in state NA were explicable in terms of greater disease severity, the association of trait NA and symptoms was independent of objective disease. The trait NA complaint association was also independent of state NA and hence not attributable to trait-elicited state affect. Greater trait NA was associated with biases in complaining during but not before illness. This suggested failure to discriminate between symptoms rather than increased sensitivity or hypochondriacal response.